Alzheimer's Disease Hallmarks: Beta-Amyloid in the Hippocampus of TgF344-AD Rats and its Relation to Cognitive Impairment
Author
Christensen, Vibeke Kjellberg
Term
4. term
Education
Publication year
2021
Submitted on
2021-05-27
Pages
42
Abstract
Alzheimer’s disease has been known for over 100 years and affects more people as populations age. There is still no cure or reliable prevention, and the full causes remain unclear. Research has advanced, including brain imaging and mapping that allow study of the disease in living humans. Treatment development often relies on animal models, yet many therapies that work in animals fail in humans, possibly because the models do not capture the full complexity of the disease. A newer, promising model is the TgF344-AD rat (developed in 2013 by Cohen and colleagues), which shows more Alzheimer-like features than most other models, including brain pathology, cognitive problems, and neuropsychiatric symptoms. However, more work is needed to understand this model. This thesis summarizes current knowledge about Alzheimer’s disease and the TgF344-AD model, and examines beta-amyloid in the hippocampus (a brain area important for memory) using immunohistochemistry, a staining method that uses antibodies to detect specific proteins in tissue. It also compares beta-amyloid levels with memory performance measured by the Barnes Maze, a spatial memory test in which a rat finds an escape hole on a circular platform. The study includes eight 10-month-old TgF344-AD rats and eight age- and sex-matched Fisher 344 wildtype littermates. A clear genotype difference in beta-amyloid is found: wildtype rats have virtually none, while transgenic rats have plaques covering on average 9.84% of the hippocampus. These findings are compared with data from a previous rat study, and the use of immunohistochemistry is discussed. For memory, there is no correlation between the amount of hippocampal beta-amyloid and Barnes Maze performance, similar to results seen in human Alzheimer’s studies. Potential confounding factors, including neuropsychiatric symptoms (changes in mood and behavior), are considered. Overall, the results support the TgF344-AD rat as a promising, more integrative model whose disease course resembles several aspects of human Alzheimer’s disease.
Alzheimers sygdom har været kendt i over 100 år og rammer flere, i takt med at befolkningen bliver ældre. Der findes stadig ingen kur eller sikker forebyggelse, og de fulde årsager er ikke endeligt afklaret. Forskningen har dog gjort fremskridt, blandt andet gennem hjerneafbildning og kortlægning, som gør det muligt at studere sygdommen i levende mennesker. Udvikling af behandlinger bygger ofte på dyremodeller, men mange lovende behandlinger, der virker i dyr, fejler i mennesker. En mulig forklaring er, at dyremodellerne ikke fuldt ud fanger sygdommens kompleksitet. En nyere og lovende model er TgF344-AD rotten (udviklet i 2013 af Cohen og kolleger), som udviser flere træk ved Alzheimers end de fleste andre modeller, herunder hjernemæssige forandringer, kognitive problemer og neuropsykiatriske symptomer. Der er dog stadig mere at lære om denne model. Formålet med dette speciale er at samle aktuel viden om Alzheimers sygdom og TgF344-AD modellen samt at undersøge forekomsten af beta-amyloid i hippocampus (et hukommelsesområde i hjernen) ved hjælp af immunhistokemi, en farvningsmetode der bruger antistoffer til at påvise specifikke proteiner i væv. Derudover sammenlignes mængden af beta-amyloid med hukommelsesproblemer målt med Barnes Maze, en rumlig hukommelsestest hvor rotten finder et flugthul på en rund plade. Studiet omfatter otte 10 måneder gamle TgF344-AD rotter og otte alders- og kønsmatchede Fisher 344 vildtype-kuldssøskende. Der findes en tydelig forskel i beta-amyloid mellem genotyperne: vildtyperne har stort set ingen, mens transgene rotter i gennemsnit har plakker, der dækker 9,84 % af hippocampus. Fundene sammenlignes med data fra en tidligere rotteundersøgelse, og anvendelsen af immunhistokemi diskuteres. For hukommelse ses ingen sammenhæng mellem mængden af beta-amyloid i hippocampus og præstation på Barnes Maze, hvilket ligner resultater fra studier af mennesker med Alzheimers sygdom. Mulige forstyrrende faktorer, herunder neuropsykiatriske symptomer (ændringer i humør og adfærd), drøftes. Samlet set understøtter resultaterne, at TgF344-AD rotten er en lovende og mere integrativ model, hvis sygdomsforløb på flere punkter ligner det, man ser hos mennesker med Alzheimers.
[This apstract has been rewritten with the help of AI based on the project's original abstract]
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